Connective tissue macromolecules are basic components in cardiovascular structures which play an important role in maintaining the integrity of the cardiovascular system. The carbohydrate-protein macromolecules of connective tissue are of specific interest and changes of these materials in the arterial wall in human and experimental atherosclerosis are being studied. Proteoglycans, the more native state of glycosaminoglycans (GAG) in the arterial wall matrix, are being characterized in bovine aorta. Two proteoglycan-hyaluronate complexes, molecular weights of 800,000 and 250,000 Daltons, have been isolated and found to have varying proportions of GAG. Primarily the proteoglycan contains chondroitin sulfates and dermatan sulfate as a hybrid. The amount of hyaluronic acid in the complexes varied. In contrast to chondromucoprotein, aggregation does not seem to occur and no glycoprotein materials have been identified as part of the complex material. The interaction of proteoglycans with serum lipoproteins is under study as a potential mechanism in the development of human atherosclerotic lesions. Specific enzymatic digestion with collagenase and elastase releases varying amounts and different GAG, suggesting proteoglycans or GAG interact with fibrous structures, collagen and elastin. In the complexing with lipoproteins, two molecular weight species of hyaluronic acid, 400,000 and 90,000 Daltons, were found in large quantities, unexpectedly. Studies of the complexes of lipoproteins, hyaluronic acid and fibrous structures suggest an interaction or possible covalent linkage with fibrous proteins of the arterial wall. In other studies, since GAG have been used for treating human atherosclerosis, biologic properties and the antiatherogenic affects of drugs used clinically are being evaluated. Heparin and Heparin-like compounds (from Italy) given parenterally decrease the amount of vascular lesions in experimental atherosclerosis.